1. Field of the Invention
The present invention relates to a therapeutic or/and diagnostic substance. Furthermore it relates to an expression vector, to a composition comprising the afore-mentioned substance or/and the aforementioned expression vector, a method for diagnosing a tumor disease or/and an infectious disease in a living being, as well as to a method for the treatment of a tumor disease or/and of an infection in a living being.
2. Related Prior Art
Therapeutic and diagnostic substances which are used in the therapy and diagnosis of tumor diseases or infections, are generally known in the art.
A therapeutic approach in the treatment of tumor and infectious diseases relates to the administration of drugs which cause a damage, necrosis, or growth inhibition of the tumor cells or infected cells.
The so-called cytostatics constitute a group of mostly synthetically produced and chemical heterogeneous substances which have toxic defects on different biological cells, and inhibit cell growth and cell division.
The cytostatic or cytotoxic substances, respectively, which are available so far, do not have a selective effect on tumor cells but harm normal tissue as well. Especially affected are tissues with high cell division rates, as, for example, gonads, hair follicles, and cells of the blood-forming system. An overview about the development of cytostatic is given in S. N. Gardner and H. Fernandes (2004), “Cytostatic Anticancer Drug Development”, J. Exp. Ther. Oncol., pages 9 to 18.
Improvements in the treatment and diagnosis of tumor and infectious diseases were made after the discovery of antigens which are expressed on the surface of infected or transformed cells. Such surface proteins on tumor cells are referred to as so-called tumor antigens. Based on these findings, there are efforts to develop substances which specifically recognize these tumor antigens and thereupon mediate a selective attack on the tumor cell. This is for example attempted by means of antibodies specific for these tumor antigens, which are coupled to cytotoxic substances. Another corresponding approach relates to a specific stimulation of the immune system against tumor cells by administering these tumor antigens which can be modified, or by the direct application of so-called tumor vaccines containing these tumor antigens. An overview about this therapeutic approach is given in Joseph N. Blattmann and Philip D. Greenberg (2004), “Cancer Immunotherapy: A Treatment for the Masses”, Science, Vol. 305, pages 200 to 205.
However, a disadvantage of this approach is that by most of the currently known tumor antigens malignant cells cannot be distinguished from benign neoplasms or even from normal cells, so that a targeted attack on malignant cells is not possible with such antigens or will not give satisfactory results. Furthermore, there are infected and transformed cells described in the art, which show no special immunogenicity at all. In this case, a distinction between these cells and normal cells and, therefore, a targeted therapeutic intervention by the means of surface markers is not possible.
It is also known in the art that in tumor cells regulatory mechanisms are altered when compared with normal cells. The reason for this could be a genetic alteration of signal transduction factors. A summary of genetic alterations in tumor cells can be found in Douglas Hanahan and Robert A. Weinberg (2000), “The Hallmarks of Cancer”, Cell, Vol. 100, pages 57 to 70.
Among experts it is known that in certain tumor cells permanent or increased growth signals of structurally intact but amplified surface receptor kinases are transduced into the cell, whereas in normal cells growth impulses are only induced at specific times. Equally, a huge number of tumors have been described to show activating mutations of intracellular factors of the signal transduction cascade, such as for example mutations in the ras protein, a monomeric GTPase having proliferation regulating activity. The ras protein is mutated in 30% of human tumors. This mutation that is mainly described for exocrine pancreas carcinoma and in colon carcinoma, causes the loss of the hydrolytic activity of the ras protein resulting in a permanent active and proliferation-stimulating form of this protein. Also observed in tumor cells is the inhibition or knockout of growth inhibitory factors like the retinoblastoma (Rb) or the p53 protein, the so-called tumor suppressors. A110 described in the art is an alteration of the telonerase activity in tumor cells which is connected with the acquisition of immortalizing properties. These cells have the property that they, unlike normal cells, can be permanently cultivated in cell culture. Further summarizing reports thereto can be found in William C. Hahn and Robert A. Weinberg (2002), “Rules for Making Human Tumor Cells”, N. Engl. J. Med., Vol. 347, No. 20, pages 1593 to 1603; or in William C. Hahn and Robert A. Weinberg (2002), “Modelling the Molecular Circuitry of Cancer”, Nat. Rev. Cancer, Vol. 2(5), pages 331 to 341.
Irish et al. (2004), “Single Cell profiling of Potentiated Phospho-Protein Networks in Cancer Cells”, Cell, Vol. 118, pages 217 to 228, have discovered that several transduction mechanisms which are controlled by the phosphorylation of signal molecules are altered in tumor cells. On account of these findings, the authors drew up tumor-specific multidimensional molecular phospho profiles. However they do not describe in detail how exactly the signal transduction factors in tumor cells are altered in comparison to those in non-tumor cells. Further there is no description about the relation between the altered signal molecules and the cell cycle, since the experiments described in this document were only performed over a very short time period.
Despite of these discoveries regarding altered signal transduction mechanisms in tumor cells, the experts have so far failed in providing a substance that therapeutically or/and diagnostically benefits from these alterations.